The maintenance of cardiac performance would be a positive survival value in burn shock and other circulatory shock states. Myocardial Depressant Factor (MDF) has been hypothesized to be an important etiologic agent for cardiac dysfunction in shock states. It has further been proposed to be a unifying mechanism for the development of irreversible shock. This shock remains one of the most controversial hypothesis explaining the cardiovascular collapse of irreversible circulatory shock. MDF has been detected in high quantities in the plasma of dogs subjected to splanchnic artery occlusion shock and has been proposed as the mechanism for resuscitative failure in severe burn injury. MDF activity is detected in the cat isolated papillary muscle preparation under isotonic or isometric conditions. This project seeks to define the pathophysiological role of MDF in the development of irreversible shock. This will necessitate the isolation, purification and structural analyses of MDF. Preliminary results in our laboratory indicate the existence of MDF-like material in the sera of dogs subjected to two different shock models and suggest this activity is exerted by elevated levels of leucine and by another yet unidentified higher molecular weight component. We will analyze the plasma of burn patients and experimentally burned animals for the presence of MDF and leucine. In order to ascertain the role of MDF in the etiology of circulatory shock, a specific antibody against MDF will be raised and administered to dogs subjected to a variety of shock models. By selectively inactivating MDF in the circulation in a variety of shock states, it should be possible to definitely ascertain the role of MDF in the development of irreversible shock. If, after selectively inactivating circulating MDF, the experimentally shocked animals survive or live longer than the appropriately treated controls, then these data would indicate that MDF contributes significantly to terminal cardiovascular collapse in shock. These results would confirm the hypothesis that MDF is a universal inducer of circulatory collapse in shock.